It is planned to develop a system of protein markers to identify new genetic loci in the mouse. These markers will be used to expand the mouse genetic map to the point where an appreciable percentage of the genome can be covered in a single cross. The method involves 2D-electrophoresis of cytosols of mouse organs by first isoelectrofocusing the homogenate in urea, or otherwise separating the proteins or subunits by charge, followed by a second dimension in which the proteins or subunits are separated by molecular weight. Each organ gives a characteristic protein pattern. Patterns for the same organ from different mouse strains show a number of genetically determined differences. Animals from crosses between strains will be phenotyped for each difference simultaneously and the newly discovered loci will be mapped on the current map. Once such loci are mapped they will provide an efficient method for mapping other genes. Using liver and kidney cytosols and plasma at least eight differences can already be scored on DBA/2 x C57BL/6 crosses. Further new genetic loci will be found by studying organellar proteins, cytosol proteins from other organs and by using radioactive labelling techniques to look for turnover mutants.